indication

For the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance

pharmacology

Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic.

mechanism of action

Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

toxicity

Side effects include agitation, coma, confusion, convulsions, dilated pupils, disturbed concentration, drowsiness, hallucinations, high fever, irregular heart rate, low body temperature, muscle rigidity, overactive reflexes, severely low blood pressure, stupor, vomiting

biotransformation

Hepatic

absorption

Rapid absorption

half life

11-18 hrs

drug interactions

Abarelix: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Almotriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Amiodarone: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Amitriptyline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Amobarbital: The barbiturate, Amobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Amobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Amoxapine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Amprenavir: The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Amprenavir is initiated, discontinued or dose changed.

Arsenic trioxide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Atazanavir: The strong CYP3A4 inhibitor, Atazanavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Atazanavir is initiated, discontinued or dose changed.

Bromocriptine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Buspirone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Butabarbital: The barbiturate, Butabarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Butabarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Butalbital: The barbiturate, Butalbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Butalbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Cabergoline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Chlorpromazine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Chlorpromazine, a strong CYP2D6 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Caution should be used during concomitant therapy.

Cimetidine: Cimetidine may increase the effect of tricyclic antidepressant, trimipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if cimetidine is initiated, discontinued or dose changed.

Cinacalcet: The strong CYP2D6 inhibitor, Cinacalcet, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Cinacalcet is initiated, discontinued or dose changed.

Cisapride: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Citalopram: The SSRI, Citalopram, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Citalopram is initiated, discontinued or dose changed.

Clarithromycin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Clarithromycin, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Concomitant therapy should be used with caution.

Clomipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Clonidine: Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Clonidine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Clonidine should be withdrawn very gradually to reduce the risk of hypertensive crisis.

Cocaine: The strong CYP2D6 inhibitor, Cocaine, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate.

Darunavir: The strong CYP3A4 inhibitor, Darunavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Darunavir is initiated, discontinued or dose changed.

Dasatinib: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Delavirdine: The strong CYP3A4/CYP2D6 inhibitor, Delavirdine, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Delavirdine is initiated, discontinued or dose changed.

Desipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dexmedetomidine: Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Dexmedetomidine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Dexmedetomidine should be withdrawn very gradually to reduce the risk of hypertensive crisis.

Dextromethorphan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dihydroergotamine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Disopyramide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Dofetilide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Dolasetron: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Domperidone: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Donepezil: Possible antagonism of action

Doxepin: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Droperidol: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Duloxetine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Eletriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Epinephrine: Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Epinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Ergoloid mesylate: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Ergonovine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Ergotamine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Erythromycin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Escitalopram: The SSRI, Escitalopram, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Escitalopram is initiated, discontinued or dose changed.

Fenoterol: The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of fenoterol.

Flecainide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Fluconazole: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Fluconazole, a strong CYP2C19 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Concomitant therapy should be used with caution.

Fluoxetine: The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, trimipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used cautiously.

Flupenthixol: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Fluvoxamine: The strong CYP2C19 inhibitor, fluvoxamine, may decrease the metabolism and clearance of trimipramine, a CYP2C19 substrate. Additive modulation of serotonin activity may also increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome and changes in therapeutic and adverse effects of trimipramine if fluvoxamine is initiated, discontinued or dose changed.

Fosamprenavir: The strong CYP3A4 inhibitor, Fosamprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Fosamprenavir is initiated, discontinued or dose changed.

Foscarnet: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Frovatriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Furazolidone: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Galantamine: Possible antagonism of action

Gatifloxacin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Gemfibrozil: The strong CYP2C19 inhibitor, Gemfibrozil, may decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Gemfibrozil is initiated, discontinued or dose changed.

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Guanabenz: Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Guanabenz. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Guanabenz should be withdrawn very gradually to reduce the risk of hypertensive crisis.

Guanethidine: The tricyclic antidepressant, trimipramine, decreases the effect of guanethidine.

Guanfacine: Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Guanfacine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Guanfacine should be withdrawn very gradually to reduce the risk of hypertensive crisis.

Halofantrine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Haloperidol: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Ibutilide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Imatinib: The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Imatinib is initiated, discontinued or dose changed.

Imipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Indapamide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Indinavir: The strong CYP3A4 inhibitor, Indinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Indinavir is initiated, discontinued or dose changed.

Isocarboxazid: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Isoniazid: The strong CYP3A4/CYP2C19 inhibitor, Isoniazide, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Isoniazid is initiated, discontinued or dose changed.

Isradipine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Itraconazole: The strong CYP3A4 inhibitor, Itraconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Itraconazole is initiated, discontinued or dose changed.

Ketoconazole: The strong CYP3A4 inhibitor, Ketoconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Ketoconazole is initiated, discontinued or dose changed.

Lapatinib: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Levofloxacin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Linezolid: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Lithium: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Lopinavir: The strong CYP3A4/CYP2D6 inhibitor, Lopinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Lopinavir is initiated, discontinued or dose changed.

Loxapine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Maprotiline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Mefloquine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Meperidine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Mephentermine: Trimipramine may increase the vasopressor effect of the alpha1-agonist, Mephentermine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Mesoridazine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Methadone: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Methohexital: The barbiturate, Methohexital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Methohexital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Methoxamine: Trimipramine may increase the vasopressor effect of the alpha1-agonist, Methoxamine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Methylergonovine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Miconazole: The strong CYP3A4/2D6/2C19 inhibitor, Miconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/2D6/2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Miconazole is initiated, discontinued or dose changed.

Midodrine: Trimipramine may increase the vasopressor effect of the alpha1-agonist, Midodrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Mirtazapine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Moclobemide: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Modafinil: The strong CYP2C19 inhibitor, Modafinil, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Modafinil is initiated, discontinued or dose changed.

Moxifloxacin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Naratriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Nefazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Nefazodone, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nefazodone is initiated, discontinued or dose changed.

Nelfinavir: The strong CYP3A4 inhibitor, Nelfinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nelfinavir is initiated, discontinued or dose changed.

Nicardipine: The strong CYP3A4 inhibitor, Nicardipine, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nicardipine is initiated, discontinued or dose changed.

Nilotinib: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Norepinephrine: Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Norepinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Norfloxacin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Nortriptyline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Octreotide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Omeprazole: The strong CYP2C19 inhibitor, Omeprazole, may decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Omeprazole is initiated, discontinued or dose changed.

Orciprenaline: The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of orciprenaline.

Paroxetine: The SSRI, Paroxetine, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Paroxetine is initiated, discontinued or dose changed.

Pentamidine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Pentobarbital: The barbiturate, Pentobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Pentobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Perflutren: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Pergolide: Increased risk of serotonin syndrome. Pergolide, a strong CYP2D6 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Monitor for symptoms of serotonin syndrome and changes in Trimipramine therapeutic and adverse effects if Pergolide is initiated, discontinued or dose changed.

Phenelzine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Phenobarbital: The barbiturate, Phenobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Phenobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Phenylephrine: Trimipramine may increase the vasopressor effect of the alpha1-agonist, Phenylephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.

Phenylpropanolamine: The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of phenylpropanolamine.

Pimozide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Posaconazole: The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Posaconazole is initiated, discontinued or dose changed.

Pramlintide: The anticholinergic effects of Trimipramine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

Probucol: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Procainamide: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Procarbazine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Promethazine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Propafenone: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Protriptyline: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Pseudoephedrine: The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of pseudoephedrine.

Quetiapine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Quinidine: Additive QTc-prolonging effects may occur, increasing the risk of serious cardiac arrhythmias. Quinidine, a CYP2D6/CYP3A4 inhibitor, may also inhibit the metabolism of Trimipramine, a CYP2D6/CYP3A4 substrate. Monitor for signs of cardiac arrhythmias and for changes in Trimipramine efficacy and toxicity if Quinidine is initiated, discontinued or dose changed.

Ranolazine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Rasagiline: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Rifabutin: The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, trimipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if rifabutin is initiated, discontinued or dose changed.

Rifampin: The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, trimipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if rifampin is initiated, discontinued or dose changed.

Risperidone: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Ritonavir: The strong CYP3A4/CYP2D6 inhibitor, Ritonavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Ritonavir is initiated, discontinued or dose changed.

Rizatriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

S-Adenosylmethionine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Saquinavir: The strong CYP3A4 inhibitor, Saquinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Saquinavir is initiated, discontinued or dose changed.

Secobarbital: The barbiturate, Secobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Secobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Selegiline: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Sertraline: The SSRI, Sertraline, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Sertraline is initiated, discontinued or dose changed.

Sibutramine: Increased risk of serotonin syndrome. Concomitant therapy is contraindicated.

Sitaxentan: The strong CYP2C19 inhibitor, Sitaxsentan, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Sitaxsentan is initiated, discontinued or dose changed.

Sotalol: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Sparfloxacin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

St. John's Wort: St. John's Wort may decrease serum concentrations of Trimipramine. Possible increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if St. John's Wort is initiated, discontinued or dose changed.

Sumatriptan: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Sunitinib: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trimipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Telithromycin: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Telithromycin, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Concomitant therapy should be used with caution.

Terbinafine: Terbinafine may decrease the metabolism and clearance of Trimipramine. Consider alternate therapy or monitor for changes in Trimipramine efficacy and toxicity if Terbinafine is initiated, discontinued or dose changed. Alteration in Trimipramine dose may be required.

Terbutaline: The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of terbutaline.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tetrabenazine: May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.

Thiopental: The barbiturate, Thiopental, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Thiopental is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Thioridazine: May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.

Thiothixene: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ticlopidine: The strong CYP2C19 inhibitor, ticlopidine, may decrease the metabolism and clearance of trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of trimipramine if ticlopidine is initiated, discontinued or dose changed.

Tizanidine: Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Tizandine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Tizandine should be withdrawn very gradually to reduce the risk of hypertensive crisis.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Tramadol: Tramadol may increase the risk of serotonin syndrome and seizures.

Tranylcypromine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimethobenzamide: Trimethobenzamide and Trimipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Triprolidine and Trimipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Trimipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of trimipramine by decreasing its metabolism. Additive QTc prolongation may also occur. Monitor for changes in the therapeutic and adverse effects of trimipramine if voriconazole is initiated, discontinued or dose changed.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zolmitriptan: Use of two serotonin modulators, such as zolmitriptan and trimipramine, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).